A multicenter, open-label, phase 2, basket study to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab in subjects with selected solid tumors

The primary objective of this study is to evaluate the **safety** and **efficacy** of SKB264 in combination with pembrolizumab for the treatment of selected solid tumors, including prostate cancer, cervical cancer, ovarian cancer, urothelial carcinoma, and endometrial cancer. This is clinically relevant as it aims to determine the potential of this combination therapy to improve treatment outcomes in these malignancies.

Secondary objectives include:

• Assessing the safety and efficacy of SKB264 in combination with pembrolizumab.
• Evaluating the **pharmacokinetics** of SKB264, which involves understanding how the body absorbs, transports, metabolizes, and excretes the drug.
• Investigating the effects of SKB264 in combination with pembrolizumab on the immune system.

The clinical trial involves a total of **217 participants** who are diagnosed with various types of cancer, including **prostate cancer**, **cervical cancer**, **ovarian cancer**, **urothelial carcinoma**, and **endometrial cancer**. The study population comprises both male and female subjects aged **18 years and older**. Participants have histologically or cytologically confirmed locally advanced or metastatic cancer or recurrent cancer. The trial population was selected based on these criteria, ensuring a focus on individuals with specific solid tumors. The study does not specify particular lifestyle considerations such as diet or physical activity. The inclusion of both genders and a wide age range reflects the trial's aim to evaluate the safety and efficacy of SKB264 in combination with pembrolizumab across a diverse group of patients. The trial also includes a vulnerable population, although specific details about this group are not provided.

The clinical trial is a multicenter, open-label, phase 2 study designed to evaluate the efficacy and safety of **SKB264** in combination with **pembrolizumab** in subjects with selected solid tumors, including prostate cancer, cervical cancer, ovarian cancer, urothelial carcinoma, and endometrial cancer. The trial employs a basket study design, allowing for the assessment of the combination therapy across multiple cancer types. The study is expected to run from June 2023 to September 2026, with an estimated duration of 24 months for each participant's involvement.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on histologically or cytologically confirmed locally advanced or metastatic cancer. The primary inclusion criteria require participants to be male or female, aged 18 years or older. Following the screening, participants will receive the investigational treatment, with regular follow-up visits scheduled to monitor safety and efficacy outcomes. The primary endpoints include the number of subjects with dose-limiting toxicities, adverse events, and discontinuation due to adverse events, as well as the proportion of subjects with a confirmed complete or partial response. Secondary endpoints will assess safety through vital signs, physical examinations, laboratory tests, and electrocardiograms, alongside antitumor activity measures such as disease control rate and progression-free survival.

The trial will conclude with an end-of-study visit, where final assessments will be conducted to evaluate the overall outcomes of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study aims to provide valuable insights into the potential benefits and risks of the combination therapy in treating various solid tumors.

The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is administered via **intravenous use**. The maximum daily dose is 400 mg, with a total maximum dose of 6800 mg over a treatment period of up to 24 months. Pembrolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02. The medication is used unmodified in the study, except for labeling and repackaging, and is manufactured by Merck Sharp & Dohme BV.

Another experimental treatment in the study is **SKB264**, also a **solution for infusion**. This medication is administered intravenously with a dosing regimen of up to 5 mg/kg per day, not exceeding a total dose of 260 mg over the course of the study, which spans up to 24 months. SKB264 is an antibody-drug conjugate developed by Sichuan Kelun-Biotech Biopharmaceutical Co. and is classified as a protein-based therapeutic agent.

In addition to the experimental treatments, the study includes several non-experimental treatments categorized as auxiliary medications. These include products classified under the ATC codes H02AB (glucocorticoids), N02BE01 (paracetamol), M01A (anti-inflammatory and antirheumatic products, non-steroids), and R06A (antihistamines for systemic use). These auxiliary treatments are not specified in terms of active substances or pharmaceutical forms and are listed with unknown routes of administration. They are included in the study protocol to support the primary experimental treatments, with no specified dosing schedules or maximum dose amounts.

The efficacy of the clinical trial will be assessed through several primary and secondary endpoints. The primary efficacy endpoints include the proportion of subjects achieving a confirmed complete response or partial response, as well as the percentage of subjects experiencing a decrease in **prostate-specific antigen** levels. These endpoints will provide insight into the therapeutic effectiveness of the combination of SKB264 and pembrolizumab in treating selected solid tumors.

Secondary efficacy assessments will focus on the disease control rate, duration of response, progression-free survival, and overall survival. These parameters will evaluate the antitumor activity of the treatment regimen. Additionally, pharmacokinetic parameters such as the area under the serum concentration curve (AUC), minimum serum concentration (Cmin), and maximum serum concentration (Cmax) will be measured to understand the drug's behavior in the body. The presence of antibodies against the study drug will also be tested, with the number of subjects showing positive anti-drug antibodies (ADA) and ADA titers being recorded.